p53 protein accumulation and genetic alterations in human giant cell tumors of bone (osteoclastomas)

Abstract Inactivation of tumor suppressor genes represents a critical determinant in the development of a large proportion of human cancers. The tumor suppressor gene p53 is the most frequently altered gene in human cancers. In the present study, p53 protein accumulation, gene mutation and the association between p53 alteration and clinicopathological parameters was analyzed in 29 giant cell tumors of bone. p53 overexpression was detected by immunohistochemistry in 23 of 29 (79%) primary tumors but not in adjacent bone tissue. p53 gene mutations in exons 5-8 were detected in 15 of 29 (52%) of the tumors by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. In 15 (52%) of 29 patient specimens, p53 immunostaining and mutations in exons 5-8 were concordant. Eleven (38%) of 29 tumors overexpressed p53 in the absence of mutations in exons 5-8. No significant association between p53 alterations and clinicopathological parameters was found. The present study represents the first report to assess p53 protein content and gene mutation in a substantial number of giant cell tumors of bone and suggests that p53 alterations play an important role in the development of this neoplasm.